Moore R, Carlson S, Madara J L
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachussets 02115.
Am J Physiol. 1989 Aug;257(2 Pt 1):G274-83. doi: 10.1152/ajpgi.1989.257.2.G274.
A highly reproducible in vitro model of intestinal epithelial injury in guinea pig ileum was used to study the structural and functional events that accompany rapid epithelial repair. This model is characterized by denudation of the villus tip followed by rapid restitution of the epithelial barrier. Using standard electrophysiological and quantitative morphometric techniques, we found that immediately after injury the number of cells lost exceeded the number of empty cell positions on the denuded basement membrane by 100%. Concurrently, cytoplasmic processes of subepithelial myofibroblasts contained condensations of microfilaments that were not apparent in controls. Additionally, villus height was diminished immediately after injury, and progressively decreased during the restitution period. In tissues that were depleted of ATP using the uncoupler dinitrophenol and in tissues functionally denervated by tetrodotoxin, villus shortening after injury was significantly reduced. Denervation also retarded functionally and structurally defined reestablishment of epithelial barrier function. These data suggest that intestinal epithelial repair is aided by energy-dependent, neurally mediated villus contraction. We speculate that the subepithelial network of myofibroblasts is responsible for this process, which effectively minimizes the denuded surface area to be reepithelialized.
我们使用一种高度可重复的豚鼠回肠肠上皮损伤体外模型，来研究伴随快速上皮修复的结构和功能变化。该模型的特点是绒毛顶端剥脱，随后上皮屏障迅速恢复。使用标准的电生理和定量形态测量技术，我们发现损伤后立即丢失的细胞数量比裸露基底膜上的空细胞位置数量多出100%。同时，上皮下肌成纤维细胞的细胞质突起含有微丝凝聚物，这在对照组中并不明显。此外，损伤后绒毛高度立即降低，并在恢复期间逐渐下降。在使用解偶联剂二硝基苯酚耗尽ATP的组织以及用河豚毒素进行功能去神经支配的组织中，损伤后绒毛缩短明显减少。去神经支配也阻碍了上皮屏障功能在功能和结构上的重新建立。这些数据表明，肠上皮修复得益于能量依赖、神经介导的绒毛收缩。我们推测，肌成纤维细胞的上皮下网络负责这一过程，该过程有效地最小化了需要重新上皮化的裸露表面积。
